The Animal Electrophysiology and Imaging Core Facility is the most used of the CTN Cores. It supports several funded projects by CTN investigators, including current ESIs, new recruits, established mentors, and investigators from other state institutions. This Core Facility will be absolutely essential for expanding collaborations throughout the state because it contains state-of-the-art equipment that is unavailable at these state institutions. We expect that a number of Exploratory Research projects will require the facility. The Animal Electrophysiology and Imaging Core Facility is not a standard capability entity, but has always been characterized by the development of innovative technologies and advances in the area. We have developed several novel technologies that allow users to ask much more sophisticated questions than would otherwise be possible, all at lower cost. The one Core allows access to sophisticated electrophysiological methods in vivo and in vitro, as well as visualization of cells and cellular processes that would be difficult to find in a single Core Facility. For example, we helped develop the new standard for patch-clamp recordings using an upright microscope, that has superior optics arid a platform that facilitates patching of up to 4 cells simultaneously. We developed the first system, using an upright microscope that allows visual patching of identified cells as well as recording population responses. This rig uses an interface chamber, which has been used by others for blind patching, but we custom designed a system with epiillumination and epifluorescence that allows an interface chamber to be attached to the platform (instead of a superfusion chamber), along with an industrial 50X objective (used for microchip design and construction), in order to visualize and patch a single cell and record population responses simultaneously. This interface chamber patch-clamp rig has a CMOS (complementary metal-oxide semiconductor) and an EMCCD (charge-coupled device) camera that allows high-speed voltage-sensitive dye imaging as well. We have also applied event related spectral perturbation (ERSP) analysis using MatLab and a high capacity, 4 processor computer to analyze population responses with great success. Our modified immunocytochemical labeling methods of single cells recorded in slices allow us to label the entire 400 um slice instead of needing to cut it into thin sections. This improves the yield and retains the cell within the slice, allowing visualization and three-dimensional reconstruction of the cell within the population at large. Perhaps most significant is our development of calcium imaging technology. By using two high-speed cameras, we can perform ratiometric sampling as fast as 2 KHz. This permits the visualization, for example, of single channel calcium oscillations in the gamma band range. An additional advantage of this Gore is a freely-moving animal evoked potential rig for startle response and evoked potentials, especially PI 3 potential recordings, the rodent equivalent of the human P50 potential, allowing parallel animal and human studies. For example, we have ongoing projects using TMS and P50 potential recordings in humans in the Human Electrophysiology Core, and parallel studies using TMS and the PI 3 potential in rodents in vivo. This Core has a fully equipped surgical suite for survival surgeries and implantation of electrodes and pumps. A separate electrophysiology rig measures cutaneous and H-reflexes, and contains 2 treadmills and 8 motorized bicycle exercise trainers for recovery from injury or disease. These are used in ongoing studies on spinal cord injury arid Amyotrophic Lateral Sclerosis.